tbuckley/cabot-search huggingface dataset:
Pharmacological Management of Hypertrophic Cardiomyopathy: From Bench to Bedside
Authors: Chiara Palandri, Lorenzo Santini, Alessia Argirò, Francesca Margara, Ruben Doste, Alfonso Bueno-Orovio, Iacopo Olivotto, Raffaele Coppini
Journal: Drugs (2022)

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare disease has hampered the design and conduct of large, randomized trials in the last 50 years, and most of the indications in the current guidelines are derived from small non-randomized studies, case series, or simply from the consensus of experts. Guideline-directed therapy of HCM includes non-selective drugs such as disopyramide, non-dihydropyridine calcium channel blockers, or β-adrenergic receptor blockers, mainly used in patients with symptomatic obstruction of the outflow tract. Following promising preclinical studies, several drugs acting on potential HCM-specific targets were tested in patients. Despite the huge efforts, none of these studies was able to change clinical practice for HCM patients, because tested drugs were proven to be scarcely effective or hardly tolerated in patients. However, novel compounds have been developed in recent years specifically for HCM, addressing myocardial hypercontractility and altered energetics in a direct manner, through allosteric inhibition of myosin. In this paper, we will critically review the use of different classes of drugs in HCM patients, starting from "old" established agents up to novel selective drugs that have been recently trialed in patients.
GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits
Authors: Simon Bossi, Dhanasak Dhanasobhon, Graham C.R. Ellis-Davies, Jimena Frontera, Marcel de Brito Van Velze, Joana Lourenço, Alvaro Murillo, Rafael Luján, Mariano Casado, Isabel Perez-Otaño, Alberto Bacci, Daniela Popa, Pierre Paoletti, Nelson Rebola
Journal: Neuron (2022)

GluN3A is an atypical glycine-binding subunit of NMDA receptors (NMDARs) whose actions in the brain are mostly unknown. Here, we show that the expression of GluN3A subunits controls the excitability of mouse adult cortical and amygdalar circuits via an unusual signaling mechanism involving the formation of excitatory glycine GluN1/GluN3A receptors (eGlyRs) and their tonic activation by extracellular glycine. eGlyRs are mostly extrasynaptic and reside in specific neuronal populations, including the principal cells of the basolateral amygdala (BLA) and SST-positive interneurons (SST-INs) of the neocortex. In the BLA, tonic eGlyR currents are sensitive to fear-conditioning protocols, are subject to neuromodulation by the dopaminergic system, and control the stability of fear memories. In the neocortex, eGlyRs control the in vivo spiking of SST-INs and the behavior-dependent modulation of cortical activity. GluN3A-containing eGlyRs thus represent a novel and widespread signaling modality in the adult brain, with attributes that strikingly depart from those of conventional NMDARs.
Solitary Abdominal Wall Metastasis From Rectal Carcinoma Revealed on FDG PET/CT
Authors: Liu Xiao, Guannan Li, Yuhao Li, Lin Li
Journal: Clinical Nuclear Medicine (2022)

Abstract Abdominal wall metastasis from rectal carcinoma is very rare. We report FDG PET/CT findings of a solitary abdominal wall metastasis from rectal carcinoma in a 40-year-old man. On FDG PET/CT, it presents as a solitary soft tissue mass in the anterior abdominal wall with an SUV max of 9.54. The final pathology supported a diagnosis of metastasis from rectal carcinoma.
Does the Effect of a 3-Year Lifestyle Intervention on Body Weight and Cardiometabolic Health Differ by Prediabetes Metabolic Phenotype? A Post Hoc Analysis of the PREVIEW Study
Authors: Ruixin Zhu, Elli Jalo, Marta P. Silvestre, Sally D. Poppitt, Teodora Handjieva-Darlenska, Svetoslav Handjiev, Maija Huttunen-Lenz, Kelly Mackintosh, Gareth Stratton, Santiago Navas-Carretero, Kirsi H. Pietiläinen, Elizabeth Simpson, Ian A. Macdonald, Roslyn Muirhead, Jennie Brand-Miller, Mikael Fogelholm, Kristine Færch, J. Alfredo Martinez, Margriet S. Westerterp-Plantenga, Tanja C. Adam, Anne Raben
Journal: Diabetes Care (2022)

To examine whether the effect of a 3-year lifestyle intervention on body weight and cardiometabolic risk factors differs by prediabetes metabolic phenotype.This post hoc analysis of the multicenter, randomized trial, PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World (PREVIEW), included 1,510 participants with prediabetes (BMI ≥25 kg ⋅ m-2; defined using oral glucose tolerance tests). Of these, 58% had isolated impaired fasting glucose (iIFG), 6% had isolated impaired glucose tolerance (iIGT), and 36% had IFG+IGT; 73% had normal hemoglobin A1c (HbA1c; <39 mmol ⋅ mol-1) and 25% had intermediate HbA1c (39-47 mmol ⋅ mol-1). Participants underwent an 8-week diet-induced rapid weight loss, followed by a 148-week lifestyle-based weight maintenance intervention. Linear mixed models adjusted for intervention arm and other confounders were used.In the available-case and complete-case analyses, participants with IFG+IGT had greater sustained weight loss after lifestyle intervention (adjusted mean at 156 weeks -3.5% [95% CI, -4.7%, -2.3%]) than those with iIFG (mean -2.5% [-3.6%, -1.3%]) relative to baseline (P = 0.011). Participants with IFG+IGT and iIFG had similar cardiometabolic benefits from the lifestyle intervention. The differences in cardiometabolic benefits between those with iIGT and IFG+IGT were minor or inconsistent in different analyses. Participants with normal versus intermediate HbA1c had similar weight loss over 3 years and minor differences in cardiometabolic benefits during weight loss, whereas those with normal HbA1c had greater improvements in fasting glucose, 2-h glucose (adjusted between-group difference at 156 weeks -0.54 mmol ⋅ L-1 [95% CI -0.70, -0.39], P < 0.001), and triglycerides (difference -0.07 mmol ⋅ L-1 [-0.11, -0.03], P < 0.001) during the lifestyle intervention.Individuals with iIFG and IFG+IGT had similar improvements in cardiometabolic health from a lifestyle intervention. Those with normal HbA1c had greater improvements than those with intermediate HbA1c.
Revascularization in stable coronary artery disease
Authors: Rasha K Al-Lamee, Michael Foley, Christopher A Rajkumar, Darrel P Francis
Journal: BMJ (2022)

Abstract Management of stable coronary artery disease (CAD) centers on medication to prevent myocardial infarction and death. Many anti-anginal medications also have benefit for reducing symptoms, and have been proven to be effective against placebo control. Before effective preventive medications were available, patients with stable CAD often underwent revascularization with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), on the plausible assumption that these procedures would prevent adverse events and reduce symptoms. However, recent randomized controlled trials have cast doubt on these assumptions. Considering results from the recent ISCHEMIA trial, we discuss the evidence base that underpins revascularization for stable CAD in contemporary practice. We also focus on patient groups at high risk of myocardial infarction and death, for whom revascularization is often recommended. We outline the areas of uncertainty, unanswered research questions, and key areas of potential miscommunication in doctor-patient consultations.
Evaluating efficacy on tumor biopsy tissue <i>ex vivo</i> before treatment for equitable cancer care.
Authors: Heli K. Patel, Zeenia Punjani, Areesha A. Charania, Zeelu H. Patel, Georgios Papachristou, Carlo M. Contreras, Allan Tsung, Karim I. Budhwani
Journal: Journal of Clinical Oncology (2022)

e13502 Background: Nearly half the world will be diagnosed with cancer. Each year, &gt; 1.7 million new cancers are diagnosed in the US. Worse, systemic therapy turns out to be ineffective in 70% of patients because those drugs do not match the patient’s tumor, imposing a substantial physical, emotional, and financial burden. Each tumor’s distinct composition and heterogeneity can result in diverse responses to the same treatment. There is a critical and urgent need to develop ex vivo personalized cancer models that match patients with the right treatment – before treatment. Here we present a low-cost ex vivo personalized cancer model to rapidly evaluate effectiveness of various therapeutics on intact core biopsy tissue obtained from a patient’s tumor. Objective: The goal of this study is to deliver multiple isolated fluid streams to spatially distinct regions (SDRs) of intact core biopsy specimens for evaluating efficacy of multiple anticancer agents simultaneously. Methods: Core biopsies were generated from xenograft and resected human tumor tissue using 18-gauge and 20-gauge spring-loaded biopsy systems. Xenografts were established using cell lines with known sensitivity and resistance profiles. Fluid streams with anticancer agents, nucleic acid stains, and mock drugs were delivered to spatially distinct regions (SDRs) on intact core biopsy specimens in our patented Personalized Oncology Efficacy Test (POET) lab-chip bioreactors. High content imaging and custom image processing algorithms were used to measure differential activity. Results: No lateral fluid surface conduction, and only minimal lateral diffusion, was observed up to 200 μm deep in tissue. Extent of observed lateral diffusion was within operational parameters of the bioreactor. Integrity of spatially distinct regions on intact core tissue was maintained. Differential activity from anticancer agents compared to mock drugs was observed and quantitatively measured using custom image processing algorithms. Conclusions: The NCI warns that “current methods to assess potential cancer treatments are cumbersome, expensive, and often inaccurate.” A personalized medicine approach, based on efficacy observed on tissue directly from the patient’s own tumor, is fundamentally better than the current approach. Low-cost next generation ex vivo cancer models that can rapidly match treatments to tumors, such as POET, could transform cancer treatment and make a significant impact on the lives of patients.
Cause of Recurrent Syncope in an Elderly Patient
Authors: Yi-Wei Cao, Hao-Yu Wu
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2022 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study
Authors: Matt D T Hitchings, Otavio T Ranzani, Margaret L Lind, Murilo Dorion, Tatiana Lang D’Agostini, Regiane Cardoso de Paula, Olivia Ferreira Pereira de Paula, Edlaine Faria de Moura Villela, Mario Sergio Scaramuzzini Torres, Silvano Barbosa de Oliveira, Wade Schulz, Maria Almiron, Rodrigo Said, Roberto Dias de Oliveira, Patricia Vieira da Silva, Wildo Navegantes de Araújo, Jean Carlo Gorinchteyn, Natalie E Dean, Jason R Andrews, Derek A T Cummings, Albert I Ko, Julio Croda
Journal: BMJ (2022)

Abstract Objective To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in São Paulo State, Brazil. Design Test negative case-control study. Setting Community testing for covid-19 in São Paulo State, Brazil. Participants Adults aged ≥18 years who were residents of São Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test. Main outcome measures RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness. Results From 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards. Conclusions Significant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.
Light-to-Moderate Alcohol Consumption Increases the Risk of Biliary Tract Cancer in Prediabetes and Diabetes, but Not in Normoglycemic Status: A Nationwide Cohort Study
Authors: Joo-Hyun Park, Jung Yong Hong, Kyungdo Han, Young Suk Park, Joon Oh Park
Journal: Journal of Clinical Oncology (2022)

To determine whether the dose-response association between alcohol consumption and the risk of biliary tract cancer (BTC), including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), differs according to glycemic status.This nationwide cohort study included 9,520,629 individuals age ≥ 20 years without a history of cancer who underwent national health screening under the Korean National Health Insurance Service in 2009. The participants were followed up until December 2018 for BTC development. Cox proportional hazard regression analysis was performed to estimate risk.During the 78.3 million person-years of follow-up, 21,079 patients were newly diagnosed with BTC. In individuals with prediabetes and diabetes, light-to-moderate alcohol consumption increased the risk of CCA (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.13 to 1.28 and aHR, 1.58; 95% CI, 1.47 to 1.69) and GBC (aHR, 1.18; 95% CI, 1.07 to 1.31 and aHR, 1.45; 95% CI, 1.28 to 1.64). In normoglycemic individuals, light-to-moderate alcohol consumption was not associated with CCA or GBC risk. When heavy alcohol consumption was combined with diabetes, CCA and GBC risk increased synergistically (aHR, 2.04; 95% CI, 1.83 to 2.26; and aHR, 1.65; 95% CI, 1.33 to 2.04, respectively; all P < .001). Prediabetes and heavy alcohol consumption had a synergistic interactive effect on CCA and GBC risks (all P < .001). Comparable results were obtained for intrahepatic and extrahepatic CCA analyses.Even light-to-moderate alcohol consumption was associated with an increased risk of BTC in individuals with prediabetes and diabetes, but not in normoglycemic individuals. Complete avoidance of alcohol consumption may help reduce the risk of BTC in patients with prediabetes and diabetes, suggesting the need for individualized prevention strategies for BTC.
Causes, Angiographic Characteristics, and Management of Premature Myocardial Infarction
Authors: Loukianos S. Rallidis, Iosif Xenogiannis, Emmanouil S. Brilakis, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2022)

Among patients presenting with acute myocardial infarction (AMI), the proportion of young individuals has increased in recent years. Although coronary atherosclerosis is less extensive in young patients with AMI, with higher prevalence of single-vessel disease and rare left main involvement, the long-term prognosis is not benign. Young patients with AMI with obstructive coronary artery disease have similar risk factors as older patients except for higher prevalence of smoking, lipid disorders, and family history of premature coronary artery disease, and lower prevalence of diabetes mellitus and hypertension. Smoking cessation is by far the most effective secondary preventive measure. Myocardial infarction with nonobstructive coronary arteries is a relatively common clinical entity (10%-20%) among young patients with AMI, with intravascular and cardiac magnetic resonance imaging being key for diagnosis and potentially treatment. Spontaneous coronary artery dissection is a frequent pathogenetic mechanism of AMI among young women, requiring a high degree of suspicion, especially in the peripartum period.
Deep Learning–based Outcome Prediction in Progressive Fibrotic Lung Disease Using High-Resolution Computed Tomography
Authors: Simon L. F. Walsh, John A. Mackintosh, Lucio Calandriello, Mario Silva, Nicola Sverzellati, Anna Rita Larici, Stephen M. Humphries, David A. Lynch, Helen E. Jo, Ian Glaspole, Christopher Grainge, Nicole Goh, Peter M. A. Hopkins, Yuben Moodley, Paul N. Reynolds, Christopher Zappala, Gregory Keir, Wendy A. Cooper, Annabelle M. Mahar, Samantha Ellis, Athol U. Wells, Tamera J. Corte
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Reliable outcome prediction in patients with fibrotic lung disease using baseline high-resolution computed tomography (HRCT) data remains challenging. Objectives: To evaluate the prognostic accuracy of a deep learning algorithm (SOFIA [Systematic Objective Fibrotic Imaging Analysis Algorithm]), trained and validated in the identification of usual interstitial pneumonia (UIP)-like features on HRCT (UIP probability), in a large cohort of well-characterized patients with progressive fibrotic lung disease drawn from a national registry. Methods: SOFIA and radiologist UIP probabilities were converted to Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories (UIP not included in the differential, 0–4%; low probability of UIP, 5–29%; intermediate probability of UIP, 30–69%; high probability of UIP, 70–94%; and pathognomonic for UIP, 95–100%), and their prognostic utility was assessed using Cox proportional hazards modeling. Measurements and Main Results: In multivariable analysis adjusting for age, sex, guideline-based radiologic diagnosis, anddisease severity (using total interstitial lung disease [ILD] extent on HRCT, percent predicted FVC, DlCO, or the composite physiologic index), only SOFIA UIP probability PIOPED categories predicted survival. SOFIA-PIOPED UIP probability categories remained prognostically significant in patients considered indeterminate (n = 83) by expert radiologist consensus (hazard ratio, 1.73; P < 0.0001; 95% confidence interval, 1.40–2.14). In patients undergoing surgical lung biopsy (n = 86), after adjusting for guideline-based histologic pattern and total ILD extent on HRCT, only SOFIA-PIOPED probabilities were predictive of mortality (hazard ratio, 1.75; P < 0.0001; 95% confidence interval, 1.37–2.25). Conclusions: Deep learning–based UIP probability on HRCT provides enhanced outcome prediction in patients with progressive fibrotic lung disease when compared with expert radiologist evaluation or guideline-based histologic pattern. In principle, this tool may be useful in multidisciplinary characterization of fibrotic lung disease. The utility of this technology as a decision support system when ILD expertise is unavailable requires further investigation.
Gastric emptying study before gastric peroral endoscopic myotomy (G-POEM): can intragastric meal distribution be a predictor of success?
Authors: Francesco Vito Mandarino, Sabrina Gloria Giulia Testoni, Alberto Barchi, Gino Pepe, Dario Esposito, Lorella Fanti, Edi Viale, Paolo Biamonte, Francesco Azzolini, Silvio Danese
Journal: Gut (2022)
A Patient With Jaundice and Malaise
Authors: Brian L. Pearlman
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Myeloid FoxO1 depletion attenuates hepatic inflammation and prevents nonalcoholic steatohepatitis
Authors: Sojin Lee, Taofeek O. Usman, Jun Yamauchi, Goma Chhetri, Xingchun Wang, Gina M. Coudriet, Cuiling Zhu, Jingyang Gao, Riley McConnell, Kyler Krantz, Dhivyaa Rajasundaram, Sucha Singh, Jon Piganelli, Alina Ostrowska, Alejandro Soto-Gutierrez, Satdarshan P. Monga, Aatur D. Singhi, Radhika Muzumdar, Allan Tsung, H. Henry Dong
Journal: Journal of Clinical Investigation (2022)

Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). Hepatic inflammation results from abnormal macrophage activation. We found that FoxO1 links overnutrition to hepatic inflammation by regulating macrophage polarization and activation. FoxO1 was upregulated in hepatic macrophages, correlating with hepatic inflammation, steatosis, and fibrosis in mice and patients with NASH. Myeloid cell conditional FoxO1 knockout skewed macrophage polarization from proinflammatory M1 to the antiinflammatory M2 phenotype, accompanied by a reduction in macrophage infiltration in liver. These effects mitigated overnutrition-induced hepatic inflammation and insulin resistance, contributing to improved hepatic metabolism and increased energy expenditure in myeloid cell FoxO1-knockout mice on a high-fat diet. When fed a NASH-inducing diet, myeloid cell FoxO1-knockout mice were protected from developing NASH, culminating in a reduction in hepatic inflammation, steatosis, and fibrosis. Mechanistically, FoxO1 counteracts Stat6 to skew macrophage polarization from M2 toward the M1 signature to perpetuate hepatic inflammation in NASH. FoxO1 appears to be a pivotal mediator of macrophage activation in response to overnutrition and a therapeutic target for ameliorating hepatic inflammation to stem the disease progression from benign steatosis to NASH.